Depression is a common, life-disrupting, potentially lethal illness that can affect both sexes and all ages, and that is characterized by sadness, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy and poor concentration. These problems can become chronic or recurrent, substantially impairing an individual's ability to cope with daily life. At its most severe, depression can lead to suicide. Untreated major depression thus remains a serious public health problem ands its incidences are staggering.
The economic costs to society, and person costs to individuals and families, associated with depression are enormous. Within a 15-month period after having been diagnosed with depression, sufferers are four times more likely to die as those who do not have depression. The World Health Organization estimates that major depression is the fourth most important cause worldwide of loss in disability-adjusted life years, and will be the second most important cause by 2020.
Depression has no single cause; often, it results from a combination of factors. Whatever its cause, depression is not just a state of mind. It is related to long lasting changes in the brain, and connected to an imbalance of a type of chemical that carries signals in the brain and nerves. These chemicals are called neurotransmitters. Among the most important neurotransmitters related to depression are serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Serotonin plays a very important role in mood disorders, especially in anxiety and depression, aggression and impulsivity.
Most cases of depression can be treated with medication or psychotherapy. A variety of pharmacological agents are available for the treatment of depression. Significant success has been achieved through the use of serotonin-selective reuptake inhibitors (SSRIs), such as fluoxetine (PROZAC®), norepinephrine reuptake inhibitors (NERIs), combined serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), phosphodiesterase-4 (PDE4) inhibitors or other compounds. However, even with these options available, many patients fail to respond, or respond only partially to the treatment. Additionally, many of these agents show delayed onset of activity, so that patients are required to undergo treatment for weeks or months before receiving benefits. Most currently available antidepressants take 2-3 weeks or more to elicit a response.
Traditional therapies can also have significant side effects. For example, more than a third of patients taking SSRIs experience sexual dysfunction. Other problematic side effects include gastrointestinal disturbances, often manifested as nausea and occasional vomiting, agitation, insomnia, weight gain, onset of diabetes, prolongation of the heart rate corrected interval (QTc), agranylocytosis, etc. The side effects often discourage patients from following their recommended therapeutic regimen.
Therefore, there remains a need for the development of improved therapies for the treatment of depression and/or other mood and anxiety disorders.